Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB

Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

Severe Hemodilution - Clinical and Experimental Studies

In children, it is often desirable to minimize allogenic blood transfusion, and this thesis explores the physiology of an alternative method of managing perioperative blood loss: hemodilution with Ringer´s dextran. Methods Clinical studies: Arterial pressure, superior caval venous oxygen saturation (ScvO2) and blood lactate concentration (L) were studied during bone marrow harvesting (BMH) on 23 occasions in 19 children, 1-17 years of age, with healthy hearts and lungs. Experimental studies - A. Shivering was induced by surface cooling and the hemodynamic and metabolic responses studied in hemodiluted (Hgb = circa 50 g/L), 12-14 weeks old anesthetized pigs and their normoemic controls. B. The tolerance to progressive isovolemic anemia was studied during hypothermia in anesthetized and paralyzed pigs (32 °C) and their normothermic controls (38.5 °C). Main findings Clinical studies: BMH caused a blood loss of 26 (17-42) ml per kg body weight, and decreased the blood hemoglobin concentration (Hgb) to 54 (47- 84) g/L. ScvO2 was 72 (61-88) % in the awake child, and increased to 82 (70 - 94) % after induction of general anesthesia. During hemodilution, it decreased to 76 (60-92) %. The lowest ScvO2: 66 (55-79) % was seen after awakening the child in spite of the fact that Hgb had now increased to 70 (58-95) g/L by transfusion of the child´s own, preoperatively collected, blood. There was an increase in mean heart rate from 89 to 108 bpm during BMH. Mean L increased from 1.0 to 1.5 mmol/L but was never above the normal limit. Experimental studies: A. During shivering, oxygen consumption (VO2) increased by a mean factor of 2.9 in the hemodiluted pigs, and 3.7 in the controls (P< 0.001). Two of the former exhibited signs of myocardial hypoxia. B. Hgb at death was 14 ± 4 g/L in cooled pigs and 19 ± 3 g/L in the controls (P=0.015). Clinical implications -The healthy child tolerates extreme hemodilution (Hgb 50-70 g/L) if suitably anesthetized. The strain on the organism is greater after awakening. -The findings cannot be extrapolated to children with compromised function of the heart or lungs, who the author believes will frequently benefit from a normal-high Hgb. -Extreme hemodilution reduces oxygen delivery to the body and will, hence, decrease the tolerance to challenges with increased oxygen demand such as shivering. -Cooling is modestly protective during severe anemia

Validation of an Ultrasound Dilution Technology for Cardiac Output Measurement and Shunt Detection in Infants and Children.

To validate cardiac output measurements by ultrasound dilution technology (COstatus monitor) against those obtained by a transit-time ultrasound technology with a perivascular flow probe and to investigate ultrasound dilution ability to estimate pulmonary to systemic blood flow ratio in children

Central and mixed venous blood oxygen correlate well during acute normovolemic hemodilution in anesthetized pigs

BACKGROUND: Central venous oxygen saturation (ScvO2) and oxygen tension (PcvO2), obtained from the superior vena cava, correlate well with mixed venous (pulmonary arterial) oxygen saturation (SvO2) and tension (pvO2) when the hematocrit is normal. The present study was undertaken to assess whether extreme hemodilution affects this relation. METHODS: We compared mixed and central venous blood during graded arterial desaturation (inspired fraction of oxygen (FIO2) between 1.0 and 0.10) in 10 hemodiluted pigs, and in 10 pigs with normal hematocrit (control), during fentanyl-ketamine-pancuronium anesthesia and mechanical ventilation. RESULTS: Arterial oxygen saturation decreased from 100% at FIO2 = 1.0 to 44 +/- 12% at FIO2 = 0.10 (mean +/- SD). Venous oxygen saturation ranged from 3.5% to 97.3%. The regression coefficient between SvO2 and ScvO2 was 0.97 (R2 = 0.93, bias -2.4 +/- 5.8%) in the hemodiluted and 0.99 (R2 = 0.97, bias -3.0 +/- 5.0%) in the control group. Venous oxygen tension values ranged from 0.5 kPa to 9.5 kPa, and the regression coefficient for oxygen tension was 0.94 (R2 = 0.89, bias -0.20 +/- 0.47 kPa) in the hemodiluted and 0.99 (R2 = 0.97, bias -0.43 +/- 0.48 kPa) in the control group. The regression coefficient for pH was 0.95 in the hemodiluted and 0.98 in the control animals. CONCLUSION: The findings indicate that also during hemodilution monitoring of central venous blood oxygen may be as useful as monitoring of mixed venous blood oxygen

Lung Deposition of Nebulized Surfactant in Newborn Piglets.

It would be advantageous for the treatment of neonatal respiratory distress syndrome if effective amounts of surfactant could be delivered by nebulization

Nitrous oxide reduces inspired oxygen fraction but does not compromise circulation and oxygenation during hemodilution in pigs

BACKGROUND: The use of nitrous oxide (N2O) during hemodilution has been questioned. Nitrous oxide reduces the inspired oxygen fraction (F1O2), depresses myocardial function and may reduce cardiac output (CO) and systemic oxygen delivery (DO2SY). The aim of this study was to evaluate the importance of the effects of nitrous oxide on systemic and myocardial circulation and oxygenation during extreme, acute, normovolemic hemodilution. METHODS: Ten midazolam-fentanyl-pancuronium anesthetized pigs were exposed to 65% N2O before and after extreme isovolemic hemodilution (hematocrit 33 +/- 1% and 10 +/- 1%, respectively). Systemic and myocardial hemodynamics, oxygen delivery and consumption and blood lactate were measured before (at F1O2 1.0 and 0.35) and during N2O exposure. RESULTS: Hemodilution caused an increase in CO from 137 +/- 43 to 229 +/- 32 ml.kg-1.min-1 (P < 0.01), a decrease in systemic vascular resistance (from 42 +/- 14 to 20 +/- 4 mmHg.L-1.min-1, P < 0.05), a decrease in mean arterial blood pressure (from 119 +/- 19 to 100 +/- 26 mmHg, P < 0.05) and a decrease in DO2SY from 21.1 +/- 6.9 to 13.7 +/- 2.1 ml.kg-1.min-1 (P < 0.01). Cardiac venous blood flow increased by 135% (P < 0.01) and cardiac venous saturation from 25 +/- 6 to 41 +/- 5% (P < 0.05). After hemodilution, changing F1O2 from 1.0 to 0.35 reduced arterial blood oxygen content from 59.4 +/- 3.7 to 52.3 +/- 5.1 ml.L-1 (P < 0.01), mixed venous saturation (SvO2) from 75 +/- 9 to 47 +/- 7% (P < 0.05) and DO2SY from 13.7 +/- 2.1 to 11.9 +/- 2.3 ml.kg-1.min-1 (P < 0.05). Dissolved oxygen at F1O2 = 1.0 and F1O2 = 0.35 constituted 25.4 +/- 3.1% and 10.1 +/- 1.5%, respectively, of systemic oxygen delivery after hemodilution, compared with 10.7 +/- 1.2% and 3.9 +/- 0.5% before hemodilution (P < 0.01). Left ventricular oxygen delivery and consumption were unchanged. Exposure to N2O did not affect mean arterial blood pressure or systemic vascular resistance before or after hemodilution. After hemodilution during N2O-exposure, CO and DO2SY decreased by 9% (P < 0.01 and P < 0.05, respectively), but no changes in SvO2, systemic oxygen uptake or arterial lactate were observed. The effect of N2O on myocardial oxygenation was similar before and after hemodilution; cardiac venous blood flow, left ventricular oxygen delivery and uptake decreased, but no animals showed left ventricular lactate production. CONCLUSION: Nitrous oxide did not compromise systemic and myocardial circulation and oxygenation during acute normovolemic hemodilution in pigs. Possible adverse effects from the use of nitrous oxide during hemodilution seem to be related to a reduced F1O2, reducing the safety margin for systemic oxygen delivery

Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets.

AIM OF THE STUDY: : To investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension. METHODS: One-day old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50min(-1) and 25mmHg, respectively. They randomly received adrenaline, 10 μg kg(-1) (n=16) or placebo (n=15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls. RESULTS: CCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66-85) s vs. 77 (64-178) s [median (quartile range)] (p=0.35). Time until cerebral regional oxygen saturation (CrS(O2)) had increased to 30% was 86 (79-152) s vs. 126 (88-309) s (p=0.30). The two groups did not differ significantly in CrS(O2), heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 and 11 animals. Plasma concentration of adrenaline, 2.5min after resuming ventilation, was 498 (268-868) nmol l(-1)vs. 114 (80-306) nmol l(-1) (p=0.01). Corresponding noradrenaline concentrations were 1799 (1058-4182) nmol l(-1)vs. 1385 (696-3118) nmol l(-1) (ns). In the time controls, the concentrations were 0.4 (0.2-0.6) nmol l(-1) of adrenaline and 1.8 (1.3-2.4) nmol l(-1) of noradrenaline. CONCLUSION: The high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome

Uncompensated blood loss is not tolerated during acute normovolemic hemodilution in anesthetized pigs

Clinically, hemodilution to a hematocrit of 9% has been studied, but the effects of hypovolemia during this degree of hemodilution have not been elucidated. We studied the response to blood loss during extreme hemodilution and evaluated indicators of hypovolemia. Systemic and myocardial hemodynamics, oxygen transport, and blood lactate concentrations were measured in 12 anesthetized pigs exposed to a graded blood loss of 10, 20, 30, and 40 mL/kg. Six animals were hemodiluted (hematocrit 10.8% +/- 1.4%, mean +/- SD), and six animals served as controls (hematocrit 34.6% +/- 1.5%). Hemodilution decreased systemic oxygen delivery to 9.5 +/- 0.6 mL x kg(-1) x min(-1) (controls 21.7 +/- 3.9 mL x kg(-1) x min(-1)) (P 10 mL/kg. A decreasing arterial blood pressure, a decreasing oxygen saturation in the venous blood, and an increase in arterial blood lactate concentration were useful indicators of blood loss

Hemodilution during bone marrow harvesting in children

Eight children (1--17 yr) underwent bone marrow harvesting while in cytostatic-induced remission of their disease (leukemia [n = 6], Ewing sarcoma, and non-Hodgkin lymphoma). After the induction of general anesthesia, all patients were loaded with 10 mL/kg of a 6% high-molecular dextran solution (Macrodex — Pharmacia), which resulted in a significant preoperative decrease in hematocrit (Hct) from 32% ± 6% to 28% ± 5% (hypervolemic hemodilution) and also allowed the procedure to be performed without systemic heparinization. The blood aspirated during the harvest (24 ± 6 mL/kg; mean ± SD) was replaced with a solution of 6% dextran and Ringer's acetate solution, and the Hct decreased from 28% ± 5% to a minimum of 18% ± 3%. Immediately after the harvest, 10 mL/kg of homologous packed red blood cells was transfused, increasing Hct to 25% ± 3%. Oxygen saturation in the superior caval vein (Scvo2) decreased from 79% ± 4% before the harvest to 70% ± 3% (P < 0.01) at the end of it, and then increased to 74% ± 3% after the transfusion of homologous packed red blood cells. There was a strong linear correlation between mean values for Hct and Scvo2 during the various stages (r = 0.99). Mean heart rate decreased gradually during the procedure, from 106 ± 10 to 86 ± 7 beatslmin. There was no significant change in arterial pressure, but cardiac output measured by impedance cardiography was about 30% greater during harvesting than during undisturbed anesthesia. Pulse oximetric saturation was 99% or 100% throughout. Caval venous blood lactate and pyruvate concentrations remained within normal limits in all children. Recovery after anesthesia was uneventful, except in one child in whom severe shivering developed. H is concluded that the hemodilution resulted in a statistically but not clinically significant decrease in Scvo2 that was well tolerated by the patients as judged from hemodynamic responses as well as levels of arterial oxygen saturation (Sao2) and blood lactate